Thioredoxin-1 regulates IRE1α to ameliorate sepsis-induced NLRP3 inflammasome activation and oxidative stress in Raw 264.7 cell.
Immunopharmacol Immunotoxicol
; 45(3): 277-286, 2023 Jun.
Article
em En
| MEDLINE
| ID: mdl-36263912
ABSTRACT
Objective:
Sepsis is life-threatening organ dysfunction caused by the dysregulated host response to infection. Endoplasmic reticulum stress (ERS)-mediated inositol-requiring enzyme 1 α (IRE1α) inflammatory signaling pathway is involved in sepsis. NLRP3 inflammasome plays a key role in the activation of caspase-1 and the maturation of IL-1ß and IL-18, and finally enhances the inflammatory response. More and more evidences show that ERS is an endogenous trigger of NLRP3 inflammasome. Thioredoxin-1 (Trx-1) is a small ubiquitous thiol-1 protein with redox/inflammation modulatory properties relevant to sepsis pathogenesis. In this study, we investigated the role of Trx-1 in ERS mediated IRE1α/NLRP3 signaling pathway in Raw 264.7 cells.Methods:
Raw 264.7 cells stimulated by LPS were used to construct an inflammation model of sepsis in vitro, and the expression of proteins related to the IRE1α/NLRP3 pathway was detected through using western blot and RT-PCR. The expression of IL-18 and IL-1ß in cell supernatant was also measured by ELISA, and caspase 1 activity and ROS expression in cells were detected by kits.Results:
Our study shows that IRE1α signaling pathway related to endoplasmic reticulum stress in sepsis can activate inflammation related genes, and stimulate to produce a large number of pro-IL-1ß. At the same time, IRE1α can activate NLRP3 inflammasome and promote activation and maturation of pro-IL-1ß. Finally leads to excessive inflammatory response and ROS release, and promotes the progress of sepsis.Conclusions:
Trx-1 may inhibit NLRP3 activity and pro-IL-Iß production by inhibit IRE1α pathway of ER stress. So as to inhibit inflammatory response and ROS of cells, and play a protective role in sepsis.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tiorredoxinas
/
Sepse
/
Inflamassomos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Immunopharmacol Immunotoxicol
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
/
TOXICOLOGIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China